Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration
The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we in...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/14/4891 |
| _version_ | 1797562731068391424 |
|---|---|
| author | Daniela Caccamo Monica Currò Riccardo Ientile Elisabetta AM Verderio Angela Scala Antonino Mazzaglia Rosamaria Pennisi Maria Musarra-Pizzo Roberto Zagami Giulia Neri Consolato Rosmini Monica Potara Monica Focsan Simion Astilean Anna Piperno Maria Teresa Sciortino |
| author_facet | Daniela Caccamo Monica Currò Riccardo Ientile Elisabetta AM Verderio Angela Scala Antonino Mazzaglia Rosamaria Pennisi Maria Musarra-Pizzo Roberto Zagami Giulia Neri Consolato Rosmini Monica Potara Monica Focsan Simion Astilean Anna Piperno Maria Teresa Sciortino |
| author_sort | Daniela Caccamo |
| collection | DOAJ |
| description | The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString<sup>®</sup> technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field. |
| first_indexed | 2024-03-10T18:33:05Z |
| format | Article |
| id | doaj.art-f3e82e9278dd49eba4cd92756837aba7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:33:05Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f3e82e9278dd49eba4cd92756837aba72023-11-20T06:28:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012114489110.3390/ijms21144891Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic ConcentrationDaniela Caccamo0Monica Currò1Riccardo Ientile2Elisabetta AM Verderio3Angela Scala4Antonino Mazzaglia5Rosamaria Pennisi6Maria Musarra-Pizzo7Roberto Zagami8Giulia Neri9Consolato Rosmini10Monica Potara11Monica Focsan12Simion Astilean13Anna Piperno14Maria Teresa Sciortino15Department of Biomedical Sciences, Dental Sciences and Morpho-Functional Imaging, Polyclinic Hospital University, 98125 Messina, ItalyDepartment of Biomedical Sciences, Dental Sciences and Morpho-Functional Imaging, Polyclinic Hospital University, 98125 Messina, ItalyDepartment of Biomedical Sciences, Dental Sciences and Morpho-Functional Imaging, Polyclinic Hospital University, 98125 Messina, ItalySchool of Science and Technology, Centre for Health, Ageing and Understanding of Disease, Nottingham Trent University, Nottingham NG11 8NS, UKDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, ItalyCNR-Istituto per lo Studio dei Materiali Nanostrutturati (CNR-ISMN), Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, ItalyCNR-Istituto per lo Studio dei Materiali Nanostrutturati (CNR-ISMN), Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, ItalyNanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes-Bolyai University, T. Laurian Str. 42, 400271 Cluj-Napoca, RomaniaNanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes-Bolyai University, T. Laurian Str. 42, 400271 Cluj-Napoca, RomaniaNanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes-Bolyai University, T. Laurian Str. 42, 400271 Cluj-Napoca, RomaniaDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, ItalyThe graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString<sup>®</sup> technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field.https://www.mdpi.com/1422-0067/21/14/4891nanostring<sup>®</sup>graphenecyclodextrindoxorubicingene expressionFLIM |
| spellingShingle | Daniela Caccamo Monica Currò Riccardo Ientile Elisabetta AM Verderio Angela Scala Antonino Mazzaglia Rosamaria Pennisi Maria Musarra-Pizzo Roberto Zagami Giulia Neri Consolato Rosmini Monica Potara Monica Focsan Simion Astilean Anna Piperno Maria Teresa Sciortino Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration International Journal of Molecular Sciences nanostring<sup>®</sup> graphene cyclodextrin doxorubicin gene expression FLIM |
| title | Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration |
| title_full | Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration |
| title_fullStr | Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration |
| title_full_unstemmed | Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration |
| title_short | Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration |
| title_sort | intracellular fate and impact on gene expression of doxorubicin cyclodextrin graphene nanomaterials at sub toxic concentration |
| topic | nanostring<sup>®</sup> graphene cyclodextrin doxorubicin gene expression FLIM |
| url | https://www.mdpi.com/1422-0067/21/14/4891 |
| work_keys_str_mv | AT danielacaccamo intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT monicacurro intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT riccardoientile intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT elisabettaamverderio intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT angelascala intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT antoninomazzaglia intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT rosamariapennisi intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT mariamusarrapizzo intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT robertozagami intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT giulianeri intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT consolatorosmini intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT monicapotara intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT monicafocsan intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT simionastilean intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT annapiperno intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration AT mariateresasciortino intracellularfateandimpactongeneexpressionofdoxorubicincyclodextringraphenenanomaterialsatsubtoxicconcentration |